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• cancer/oncology
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histopathology

Our group is principally interested in the cellular and molecular mechanisms which drive cancers to progress to invasive or metastatic phenotypes. Our work in recent years has focused on the contribution of altered adhesion to this process, and has challenged the simple paradigm that decreased adhesion is a pre-requisite for cancer cell invasion (Leech AO et al, Ann Transl Med. 2015 Aug;3(13):184. doi: 10.3978/j.issn.2305-5839.2015.08.01). Specifically, we were the first to identify that overexpression of a particular adhesion protein, junctional adhesion molecule-A (JAM-A) in breast cancer patient tumour tissue was associated with increased risk of metastasis (McSherry et al, Int J Cancer. 2009 Sep 15;125(6):1343-51. doi: 10.1002/ijc.24498). We later showed that JAM-A overexpression drives cell migration (McSherry et al, Breast Cancer Res. 2011 Mar 23;13(2):R31. doi: 10.1186/bcr2853), a key early step in metastasis, and that JAM-A expression levels can regulate those of the important breast cancer oncogene human epidermal growth factor receptor-2/HER-2 (Brennan et al Oncogene. 2013 May 30;32(22):2799-804. doi: 10.1038/onc.2012.276). We have since developed novel insights into the potential contribution of JAM-A to clinical drug resistance to HER2-targeted therapies, and designed a novel small molecule inhibitor of JAM-A signalling which has shown promise in vitro and in pilot in vivo studies of murine cancer biology. We feel that JAM-A represents a novel pharmacological target of potential relevance to many cancers, and our ongoing studies will pursue in depth its contribution to tumourigenic signalling.

There are several potential projects arising from our work in the field of the contribution of JAM-A to cancer progression. All fall under the banner of translational cancer biology, wherein cell biology, molecular biology and biochemistry are used to interrogate important biological questions in a reductionist setting, with translation into more clinically-relevant spheres being accomplished by the strategic complementary usage of patient databases, patient tumour tissue microarrays, patient primary cell cultures, patient blood sample biobanks and other related resources. Sample projects envisaged are as follows, but many more are possible depending upon engagement with motivated individuals interested in disciplines like oncology, surgery, immunology, pathology or radiology:

(1) Interrogating the contribution of JAM-A signalling to sustained tumourigenicity and clinical drug resistance to HER2-targeted therapies in patients;
(2) The role of novel JAM-A-based therapeutics in a combination approach towards the molecular targeting of specific cancers;
(3) JAM-A and its influence on cancer stem cells - a new approach towards the problems of local recurrence and distant metastasis;
(4) Probing the breast intra-ductal space as a route to deliver JAM-A-based therapeutics for the local targeting of ductal carcinoma in situ, DCIS (collaboration with the Sidney Kimmel Cancer Center at Johns Hopkins).